General pharmacology最新文献

1. The effects of dopamine agonists on the immobility time in mice were examined. 2. Apomorphine (APO), bupropion (BUP), bromocriptine (BRC) and quinpirole but not SKF 38393 elicited anti-immobility effect. The effect of the agonists was decreased by the D-2 antagonist sulpiride but not by the D-1 antagonist SCH 23390. 3. In animals pretreated with reserpine, the anti-immobility effects of APO and quinpirole were potentiated, while the response of BPU was decreased and that of BRC was not changed. 4. It is concluded that D-2 dopamine receptors are involved in the anti-immobility effects of dopaminergic agents, D-2 dopamine receptors may become hypersensitive by reserpine and BUP exerts its response through indirect dopaminergic if mechanism.

1. The effects of 5 pregnane compounds isolated from the rhizomes of Mandevilla illustris were examined against bradykinin (BK), Lysyl-bradykinin (L-BK), acetylcholine (ACh) and oxytocin (Ot)-induced contractions in the isolated uteri of the rat. 2. Compounds MI 15 and MI 18 (5-40 micrograms/ml) caused a parallel and concentration-dependent rightward displacement of BK and L-BK concentration-response curves. Compound MI 21 (2.5-10 micrograms/ml) also produced a concentration-dependent displacement to the right of the BK concentration-response curve, but reduced its maximal response. Schild analysis of these data were linear (r close to 1) and furnished the following PA2 values (as G/ml): 6.0, 5.1 and 5.9, respectively. However, the slopes were significantly higher than unity. Compounds MI 25 and MI 27 (10-40 micrograms/ml) caused little or even no effect against BK and ACh responses. 3. In addition, compounds MI 18 and MI 21 (10-40 micrograms/ml) also antagonized in a concentration-dependent manner L-BK concentration-response curves. Schild plot were linear (r close to 1) and yielded the nominal pA2 values (as G/ml) of 5.0 and 5.8, respectively, but the slopes were significantly different from one. 4. Like the results obtained previously with the crude extract from M. illustris, the purified compounds from the rhizome of this plant were not selective towards kinin action since at the same range concentrations they markedly interfered with both the sensitivities and the maximal responses caused by ACh and Ot in this preparation.

1. Antiplatelet and beta-adrenoceptor activities of a set of secondary and tertiary N-methyl substituted amine analogs of trimetoquinol (TMQ, I and II, respectively) and 5,8-ethano-l-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquin oline (bicyclic isoquinoline compounds III and IV, respectively) were examined. 2. Compounds III and IV induced relaxations of guinea pig trachea which were blocked by propranolol whereas neither compound acted as an agonist nor antagonist of beta-adrenoceptors (chronotropy) in guinea pig atria. TMQ analogs (I and II) were agonists in both beta-adrenoceptor systems. 3. When tested in human platelets, compounds III and IV, like the TMQ analogs, blocked several inducers of the prostaglandin-dependent and -independent pathways, and the alpha 2-adrenoceptor-mediated pathway of platelet activation. 4. The bicyclic isoquinoline analogs (III and IV) possessed more selective beta 2-adrenoceptor stimulatory activity and equal or greater inhibitory activity against inducers of the prostaglandin-independent pathways of platelet function than the corresponding TMQ analogs (I and II). 5. These chemically novel lipophilic bicyclic compounds provide a new lead to the development of agents useful for the treatment of asthma and thrombotic disorders.

1. Apomorphine and bromocriptine induced a dose-dependent locomotion in mice. The responses of both drugs were decreased by SCH 23390 or sulpiride pretreatment. 2. Locomotor activity induced by apomorphine was increased and that of bromocriptine was decreased by reserpine. 3. SKF 38393 or quinpirole also induced locomotion. The response of SKF 38393 was decreased by reserpine. 4. Combination of SKF 38393 with bromocriptine induced a significant locomotor activity different from that of SKF 38393 or bromocriptine in reserpinized animals. 5. Combination of quinpirole with bromocriptine even decreased the response of bromocriptine in intact animals. 6. In conclusion, bromocriptine needs intact dopaminergic neurons and activation of D-1 receptor for expression of locomotion. High doses of quinpirole may induce locomotor activity possibly through D-1/D-2 receptor activation and quinpirole may potentiate the effect of bromocriptine on autoreceptor for inducing sedation.

1. The effect of free radical (superoxide and hydroxyl) and hydrogen peroxide scavengers on the formation of prostaglandin E2 by ovine placental microsomes was investigated. 2. Of the free radical scavengers tested only Mn Desferal, a low molecular weight (712 Da) superoxide scavenger, at concentrations of 0.5-5 mmol/l significantly (P less than 0.001) stimulated PGE2 formation by ovine placental microsomes. 3. This observation is consistent with the involvement of superoxide radicals in the inactivation of prostaglandin G/H synthase (PGHS). 4. The results obtained further suggest that if superoxide radicals are important regulators of PGHS activity in the ovine placenta, they are not accessible to large molecular weight free radical scavengers.

1. Rats treated with a single dose of benzpyrene when newborn and inoculated with Walker's ascitic tumor cells when 6 weeks old showed 6 and 9 days later an unequivocal increase, whereas 15 and 20 days later an unequivocal decrease, in dexamethasone binding capacity (receptor number) relative to the control, i.e. a reversion of receptor activity in the course of tumor genesis. 2. The reversion of receptor activity showed a parallelism with the increase of tumor mortality over the control. 3. The experimental observations support the conclusion that neonatal exposure to benzpyrene has a depressive effect on general resistance that is reflected (or probably caused?) among others by a decrease in the binding capacity of glucocorticoid receptors.

1. The effect of tetrodotoxin (5 microM), monensin (10 microM) and the replacement of Na+ by choline (choline medium) on the contractions of the rat testicular capsule induced by oxytocin (50 and 200 nM) have been studied. 2. The sodium channel blocker tetrodotoxin did not modify the oxytocin contraction. 3. The sodium ionophore monensin produces contraction of rat testicular capsule and reduces the oxytocin-induced contraction. The monensin contraction is inhibited by amiloride (0.1 mM). 4. Replacement of Na+ by choline increases the contraction induced by oxytocin and KCl (60 mM) but inhibits that induced by noradrenaline (3 microM). 5. The increase of contraction due to oxytocin in choline medium is inhibited by amiloride (50 microM and 1 mM) and when calcium is suppressed of the incubation medium.

1. Acetylcholine (10 micrograms/min) diminished the electrically-induced cerebral blood flow reductions. Atropine (1-2 mg) partially blocked this inhibitory effect. 2. Exogenously administered noradrenaline (1-10 micrograms) and tyramine (50-500 micrograms) reduced cerebral blood flow but this effect was unchanged by acetylcholine infusion. 3. Acetylcholine inhibited the nonadrenergic component of the electrically-induced contraction at a concentration greater than or equal to 10(-6) M and potentiated the adrenergic component at a concentration greater than or equal to 10(5) M. Atropine 10(-7) M) inhibited both of these effects. In addition, acetylcholine (10(-4) M) enhanced the electrically-evoked [3H]noradrenaline overflow. 4. These results show that: (a) acetylcholine modulates cerebrovascular sympathetic neurotransmission by acting on muscarinic receptors; and (b) the potentiating effect of acetylcholine is achieved by a mechanism involving increases in noradrenaline release.

1. Melatonin (10(-4)-10(-3) M) inhibited contractile response to 5-hydroxytryptamine (5-HT) and KCl in rat isolated aorta. 2. In the presence of verapamil but not nifedipine, melatonin failed to inhibit residual response to KCl. 3. In the aorta precontracted with 5-HT, PGF2 alpha, or KCl, melatonin (10(-6)-10(3) M) caused relaxation. Removal of endothelium only inhibited the melatonin relaxation on the 5-HT response. Methylene blue also inhibited the melatonin relaxation. 4. Nifedipine and verapamil partly inhibited the melatonin relaxation on the 5-HT response. In the absence of endothelium, verapamil but not nifedipine further inhibited the melatonin relaxation. 5. M & B 22,948 inhibited the melatonin relaxation. Melatonin potentiated the nitroglycerin relaxation. In the absence of endothelium, nitroglycerin and melatonin potentiated the relaxation by melatonin and nitroglycerin, respectively. 6. These results suggest that the mode of inhibitory action of melatonin is somewhat similar to that of verapamil. In addition, the vasorelaxing effect of melatonin on the 5-HT response is endothelium dependent and also may be related to the inhibition of cGMP metabolism.

1. Somatostatin (SS) was found to shorten the action potential of both left and right atrium, and to reduce the force of contraction of the atrium. Action potential shortening was antagonized by the potassium channel blocking drugs tacrine and apamin. They were less effective in reducing the negative inotropic effect of SS. 2. Alkylation of the intact atrium with N-ethylmaleimide abolished both the AP shortening and the negative inotropic effect of SS. 3. Pretreatment of guinea pigs with pertussis toxin abolished the negative inotropic effect of SS and reduced the AP shortening. 4. Binding studies showed there was virtually no interaction between SS and muscarinic and adenosine receptors. 5. It is suggested that the cardiac SS receptor is linked with G protein-K+ channel-adenylyl cyclase system which is analogous to but not identical with the muscarinic and adenosine receptor systems.